败血症通过激活YAP1/Serpine1/caspase-3通路诱导心肌细胞亡和心脏功能障碍
Xueyuan Long1, Yanpeng Yang1, Ke Zhou1
1Department of Cardiovascular Medicine, Chongqing University Central Hospital, Chongqing, 400014, China.
Open medicine (Warsaw, Poland)
|September 23, 2024
概括
败血症通过YAP1/Serpine1/caspase-3通路引起心脏功能障碍和亡. 一种Serpine1抑制剂在小鼠中逆转了这些效应,突出显示了败血症引起的心脏损伤的潜在治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 败血症病理生理学病理生理学
背景情况:
- 败血症显著增加了由于心肌损伤和功能障碍的死亡率.
- 心肌细胞亡与败血性心肌损伤有关,但潜在的机制尚不清楚.
研究的目的:
- 为了阐明败血症引起的心肌损伤的分子机制.
- 为了确定关键的基因和途径,涉及到败血症引起的心脏功能障碍.
- 调查针对已识别的途径的治疗潜力.
主要方法:
- 在败血症小鼠心脏中基因表达的生物信息分析.
- 在体内败血症模型 (结和穿刺) 与Serpine1抑制剂治疗.
- 使用暴露于LPS的小鼠心肌细胞来验证分子相互作用的体外研究.
主要成果:
- 降低了Serpine1表达和改变了HIPPO信号通路在败血性心脏.
- 败血症诱导心脏功能障碍,降低存活率,并增加了Serpine1和Cleaved Caspase-3.
- 塞尔平1抑制逆转了体质炎引起的心脏功能障碍和活体和体外亡.
- YAP1和Serpine1抑制调节的caspase-3表达,这表明它们有调节作用.
结论:
- 败血症通过YAP1/Serpine1/caspase-3通路诱导心肌细胞亡和心脏功能障碍.
- 向Serpine1为败血症引起的心脏损伤提供了一个潜在的治疗策略.
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